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微小RNA在肾细胞癌发病机制中的作用及其作为癌症生物标志物的诊断和预后价值。

MicroRNAs in the pathogenesis of renal cell carcinoma and their diagnostic and prognostic utility as cancer biomarkers.

作者信息

Fedorko Michal, Pacik Dalibor, Wasserbauer Roman, Juracek Jaroslav, Varga Gabriel, Ghazal Motasem, Nussir Mohamed I

机构信息

Department of Urology, University Hospital, Brno - Czech Republic.

Masaryk University Brno, Faculty of Medicine, Brno - Czech Republic.

出版信息

Int J Biol Markers. 2016 Feb 28;31(1):e26-37. doi: 10.5301/jbm.5000174.

Abstract

PURPOSE

To provide information about the role of microRNAs in the pathogenesis of renal cell carcinoma (RCC) and their diagnostic and prognostic utility as cancer biomarkers.

METHODS

A literature search was performed in the PubMed and Web of Science databases using the keywords "renal cancer/renal cell carcinoma/kidney cancer" and "miR*/miRNA*/microRNA*". Articles dealing with the role of miRNAs in the pathogenesis of RCC, diagnostic miRNAs and prognostic miRNAs were separated.

RESULTS

MiRNAs act both as oncogenes and tumor suppressors. They regulate apoptosis, cell growth, migration, invasion, proliferation, colony formation and angiogenesis through target proteins involved in several signaling pathways, and they are involved in key pathogenetic mechanisms such as hypoxia (HIF/VHL dependent) and epithelial-to-mesenchymal transition. Differentially expressed miRNAs can discriminate either tumor tissue from healthy renal tissue or different RCC subtypes. Circulating miRNAs are promissing as diagnostic biomarkers of RCC. Information about urinary miRNAs associated with RCC is sparse. Detection of a relapse is another implication of diagnostic miRNAs. The expression profiles of several miRNAs correlate with the prognosis of RCC patients. Comparison between primary tumor tissue and metastasis may help identify high-risk primary tumors. Finally, response to target therapy can be estimated thanks to differences in miRNA expression in tissue and serum of therapy-resistant versus therapy-sensitive patients.

CONCLUSIONS

Our understanding of the role of microRNAs in RCC pathogenesis has been increasing dramatically. Identification and validation of their gene targets may have direct impact on developing microRNA-based anticancer therapy. Several microRNAs can serve as diagnostic and prognostic biomarkers.

摘要

目的

提供有关微小RNA在肾细胞癌(RCC)发病机制中的作用及其作为癌症生物标志物的诊断和预后效用的信息。

方法

在PubMed和Web of Science数据库中进行文献检索,使用关键词“肾癌/肾细胞癌/肾癌”和“miR*/miRNA*/微小RNA*”。涉及微小RNA在RCC发病机制中的作用、诊断性微小RNA和预后性微小RNA的文章被分开。

结果

微小RNA既作为癌基因又作为肿瘤抑制因子发挥作用。它们通过参与多种信号通路的靶蛋白调节细胞凋亡、生长、迁移、侵袭、增殖、集落形成和血管生成,并且参与关键的发病机制,如缺氧(HIF/VHL依赖性)和上皮-间质转化。差异表达的微小RNA可以区分肿瘤组织与健康肾组织或不同的RCC亚型。循环微小RNA有望成为RCC的诊断生物标志物。关于与RCC相关的尿微小RNA的信息很少。检测复发是诊断性微小RNA的另一个用途。几种微小RNA的表达谱与RCC患者的预后相关。原发性肿瘤组织与转移灶之间的比较可能有助于识别高危原发性肿瘤。最后,由于治疗耐药与治疗敏感患者的组织和血清中微小RNA表达存在差异,因此可以评估对靶向治疗的反应。

结论

我们对微小RNA在RCC发病机制中的作用的理解正在急剧增加。对其基因靶点的鉴定和验证可能对开发基于微小RNA的抗癌治疗有直接影响。几种微小RNA可作为诊断和预后生物标志物。

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